Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials.

Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.

"I don't think that a medication is going to help someone long-term stay off opioids": Treatment and recovery beliefs of rural Vermont family members of people with opioid use disorder.

PURPOSE: Few studies have addressed beliefs about treatment for opioid use disorder (OUD) among family members of people with OUD, particularly in rural communities. This study examined the beliefs of rural family members of people with OUD regarding treatment, including medication for OUD (MOUD), and recovery. METHODS: Semi-structured qualitative interviews were conducted with rural Vermont family members of people with OUD. Twenty family members completed interviews, and data were analyzed using thematic analysis. RESULTS: Four primary themes related to beliefs about OUD treatment emerged: (1) MOUD is another form of addiction or dependency and should be used short-term; (2) essential OUD treatment components include residential and mental health services and a strong support network involving family; (3) readiness as a precursor to OUD treatment initiation; and (4) stigma as an impediment to OUD treatment and other health care services. CONCLUSIONS: Rural family members valued mental health services and residential OUD treatment programs while raising concerns about MOUD and stigma in health care and the community. Several themes (e.g., MOUD as another form of addiction, residential treatment, and treatment readiness) were consistent with prior research. The belief that MOUD use should be short-term was inconsistent with the belief that OUD is a disease. Findings suggest a need for improved education on the effectiveness of MOUD for family members and on stigma for health care providers and community members.

Cigarette smoking and cognitive task performance: Experimental effects of very-low nicotine-content cigarettes.

Reductions in the nicotine content of cigarettes decrease smoking rate and dependence severity, but effects on cognition are less well established. The potential impacts of very-low nicotine-content (VLNC) cigarettes on cognitive task performance must be evaluated, especially in vulnerable populations. The aim of the present study is to experimentally examine the effects of VLNC cigarettes on cognitive performance. Adults who smoked daily (n = 775) from three vulnerable populations (socioeconomically disadvantaged reproductive-age women, individuals with opioid use disorder, affective disorders) were examined. Participants were randomly assigned to normal nicotine content (NNC; 15.8 mg nicotine/g tobacco) or VLNC (2.4 mg/g or 0.4 mg/g) cigarettes for 12 weeks. Response inhibition (stop-signal task), working memory (n-back task; n of 2-n of 0), and cognitive interference (nicotine Stroop task) were assessed at baseline, 2, 6, and 12 weeks. Results were analyzed using mixed-model repeated-measures analyses of variance. Extended exposure to VLNC cigarettes produced no significant changes in any measure of cognitive performance compared to NNC cigarettes. Over weeks, response times on the n-back task decreased across doses. No significant effects were observed on the stop-signal or nicotine Stroop tasks. All three vulnerable populations performed comparably on all three cognitive tasks. Extended exposure to VLNC cigarettes produced no impairments in cognitive performance on any of the assessed tasks compared to NNC cigarettes. These findings are consistent with the larger literature detailing other consequences following exposure to VLNC cigarettes and are encouraging for the adoption of a nicotine-reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Changes in weight among individuals with psychiatric conditions or socioeconomic disadvantage assigned to smoke very low nicotine content cigarettes.

Nicotine abstinence leads to weight gain, which could be an unintended consequence of a nicotine reduction policy. This secondary analysis used weekly assessments of weight and ratings of "increased appetite/hunger/weight gain" collected in three 12-week, randomized controlled trials evaluating the effects of cigarettes differing in nicotine dose (15.8, 2.4, or 0.4 mg/g) among individuals with affective disorders, opioid use disorder (OUD), and socioeconomically disadvantaged women. Linear mixed models tested differences by dose and time. Analyses first collapsed across populations and then separated out individuals with OUD because biomarkers suggested they used substantially more noncombusted nicotine. Across populations, weight increased significantly over time, averaging 1.03 kg (p < .001), but did not vary by dose nor was there any interaction of dose/time. "Increased appetite/hunger/weight gain" ratings increased significantly as a function of dose, with differences between low and high doses (1.95 and 1.73, respectively, p = .01), but not by time nor any interaction. In the combined group of individuals with affective disorders and socioeconomically disadvantaged women, weight and "increased appetite/hunger/weight gain" ratings increased significantly by dose, with differences between low and high doses (1.43 vs. 0.73 kg, p = .003 and 2.00 vs. 1.76, p = .02, respectively). Among individuals with OUD, there were no significant effects of any kind on either outcome. Individuals with affective disorders and socioeconomically disadvantaged women gained weight and reported more subjective appetite/weight gain when given 0.4, but not 2.4 mg/g cigarettes, despite comparable decreases in nicotine exposure. However, neither change was clinically significant, suggesting minimal short-term adverse consequences of a nicotine reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Statewide Trends in Buprenorphine Prescribing in Rural and Nonrural Vermont: Analysis of Population-based Patient Pharmacy Claims.

IMPORTANCE: Opioid-related mortality rates have risen dramatically over the past decade, and office-based opioid treatment using buprenorphine offers hope for combatting this trend. Vermont's policymakers, health care systems, and treatment providers have worked to expand access to treatment throughout the rural state. OBJECTIVE: The objective of the current study was to characterize the trends in the number of buprenorphine prescribers and the number of patients per prescriber in Vermont over the past decade (2010-2020). METHODS: We used Vermont's all-payer claims database to identify patients with buprenorphine claims between 2010 and 2020 and their prescribers. We conducted analyses of trends in the number of prescribers treating different numbers of patients, the number of patients treated by prescribers in those categories, and the number of rural (vs nonrural) patients filling buprenorphine prescriptions. We used Z tests to determine if there were statistical differences between trends. RESULTS: The number of buprenorphine prescribers treating 10+ patients grew more rapidly than other prescriber groups ( P < 0.001). Nearly half of Vermont patients in 2020 were treated by 33 high-volume prescribers who treated 100 or more patients with buprenorphine. The number of patients filling buprenorphine prescriptions in Vermont increased by 98% between 2010 and 2020, with greater increases seen among rural than nonrural residents (107% vs 72%; P = 0.008). CONCLUSIONS AND RELEVANCE: Since 2010, Vermont has increased utilization of its office-based opioid treatment capacity, particularly in rural counties.

Technology-Assisted Buprenorphine Treatment in Rural and Nonrural Settings: Two Randomized Clinical Trials.

Importance: Expansion of opioid use disorder treatment is needed, particularly in rural communities. Objective: To evaluate technology-assisted buprenorphine (TAB) efficacy (1) over a longer period than previously examined, (2) with the addition of overdose education, and (3) among individuals residing in rural communities. Design, Setting, and Participants: Two parallel, 24-week randomized clinical trials were conducted at the University of Vermont between February 1, 2018, and June 30, 2022. Participants were adults with untreated opioid use disorder from nonrural (trial 1) or rural (trial 2) communities. These trials are part of a programmatic effort to develop TAB protocols to improve treatment availability in underserved areas. Interventions: Within each trial, 50 participants were randomized to TAB or control conditions. Participants in the TAB group completed bimonthly visits to ingest medication and receive take-home doses via a computerized device. They received nightly calls via an interactive voice response (IVR) system, IVR-generated random call-backs, and iPad-delivered HIV, hepatitis C virus (HCV), and overdose education. Control participants received community resource guides and assistance with contacting resources. All participants received harm reduction supplies and completed monthly assessments. Main Outcomes and Measures: The primary outcome was biochemically verified illicit opioid abstinence across monthly assessments. Secondary outcomes included self-reported opioid use in both groups and abstinence at bimonthly and random call-back visits, treatment adherence, satisfaction, and changes in HIV, HCV, and overdose knowledge among TAB participants. Results: Fifty individuals (mean [SD] age, 40.6 [13.1] years; 28 [56.0%] male) participated in trial 1, and 50 (mean [SD] age, 40.3 [10.8] years; 30 [60.0%] male) participated in trial 2. Participants in the TAB group achieved significantly greater illicit opioid abstinence vs controls at all time points in both trial 1 (85.3% [128 of 150]; 95% CI, 70.7%-93.3%; vs 24.0% [36 of 150]; 95% CI, 13.6%-38.8%) and trial 2 (88.0% [132 of 150]; 95% CI, 72.1%-95.4%; vs 21.3% [32 of 150]; 95% CI, 11.4%-36.5%). High abstinence rates were also observed at TAB participants' bimonthly dosing visits (83.0% [95% CI, 67.0%-92.0%] for trial 1 and 88.0% [95% CI, 71.0%-95.0%] for trial 2). Treatment adherence was favorable and similar between trials (with rates of approximately 99% for buprenorphine administration, 93% for daily IVR calls, and 92% for random call-backs), and 183 of 187 urine samples (97.9%) tested negative for illicit opioids at random call-backs. iPad-delivered education was associated with significant and sustained increases in HIV, HCV, and overdose knowledge. Conclusions and Relevance: In these randomized clinical trials of TAB treatment, demonstration of efficacy was extended to a longer duration than previously examined and to patients residing in rural communities. Trial Registration: ClinicalTrials.gov Identifier: NCT03420313.

US state laws relevant to incentives for health behavior: A qualitative analysis.

Contingency management (CM) involves provision of incentives for positive health behaviors via a well-defined protocol and is among the most effective treatments for patients with substance use disorders (SUDs). An understanding of laws affecting incentives for health behaviors and outcomes, including contexts in which incentives are already permitted, could inform efforts to disseminate CM. We conducted a systematic NexisUni legal database review of state statutes and regulations effective during 2022 to identify (a) laws that explicitly permit or prohibit delivery of incentives to patients, employees, or insurance beneficiaries for SUD-specific behaviors or outcomes, and (b) laws that explicitly permit delivery of incentives for any health behaviors or outcomes. We identified 27 laws across 17 jurisdictions that explicitly permit delivery of incentives for SUD-related behaviors or outcomes, with most occurring in the context of wellness programs. No state laws were identified that explicitly prohibit SUD-specific incentives. More broadly, we identified 57 laws across 29 jurisdictions permitting incentives for any health outcomes (both SUD- and non-SUD-related). These laws occurred in the contexts of wellness programs, K-12/early childhood education, government public health promotion, and SUD treatment provider licensing. Considering the urgent need to expand evidence-based SUD treatment in rural and underserved areas throughout the US, these findings could inform efforts to develop laws explicitly permitting provision of incentives in SUD care and enhance efforts to disseminate CM more broadly.

Prolonged exposure therapy for PTSD in individuals with opioid use disorder: A randomized pilot study.

OBJECTIVE: Nearly all individuals with opioid use disorder (OUD) report lifetime trauma exposure and one-third meet diagnostic criteria for posttraumatic stress disorder (PTSD). Although prolonged exposure (PE) therapy is a first-line treatment for PTSD, little is known about the effects of PE in individuals with co-occurring OUD. Furthermore, its efficacy is commonly undermined by poor therapy attendance. This pilot study evaluated the feasibility and initial efficacy of a novel PE protocol for improving PE attendance and PTSD symptoms among buprenorphine- or methadone-maintained adults with PTSD. METHOD: Thirty participants with co-occurring PTSD and OUD were randomized to receive either: (a) continued medications for OUD (MOUD) treatment as usual (TAU), (b) Prolonged Exposure therapy (PE), or (c) PE with financial incentives delivered contingent upon PE session attendance (PE+). Primary outcomes included PE session attendance, PTSD symptom severity, and use of opioids other than prescribed MOUD. RESULTS: PE+ participants attended significantly more therapy sessions vs. PE (87% vs. 35%; p <.0001). PTSD symptom reductions were also significantly greater in the PE+ vs. TAU group (p =.046). Participants in the two PE conditions submitted significantly fewer urine samples that tested positive for opioids than TAU participants (0% vs. 22%; p =.007). CONCLUSIONS: These findings provide preliminary support for the efficacy of PE+ for improving PE attendance and PTSD symptoms without prompting opioid relapse in individuals with co-occurring PTSD and OUD. These promising results justify a larger scale randomized clinical trial to more rigorously evaluate this novel treatment approach.

The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations.

AIM: While accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic. METHODS: A web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (eg social distancing, mask wearing) were examined. RESULTS: Among 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9 ± 1.0 versus 11.6 ± 1.0; p < .001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4 ± 1.4 to 13.3 ± 1.4, p = .024) as did those with higher levels of anxiety (from 11.5 ± 1.1 to 13.6 ± 1.1, p < .001). CONCLUSIONS: Smoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use. IMPLICATIONS: Individuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.

Potential effects of nicotine content in cigarettes on use of other substances.

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.